A schizophrenia treatment might be the special ingredient in a
one-two punch to combat late-stage lung cancer.

Researchers from Case Western Reserve University School of Medicine
and Mount Sinai School of Medicine found that the anti-psychotic
medication trifluoperazine can reactivate a gene pathway involved in
tumor suppression that's normally turned off in lung cancer
patients.

When combined with the targeted lung cancer drug erlotinib, it
could be a potent treatment, the researchers
(http://www.jci.org/articles/view/62058) said on Friday in the Journal
of Clinical Investigation.

Through experiments in human cells, human lung cancer tissue and
mouse lung tissue, the team found that trifluoperazine was able to stop
the product of a gene called FOXO1 from being taken out of a tumor
cell's nucleus. By keeping FOXO1 in the nucleus of the cell, it can
activate KFL6, another gene that kicks of a molecular signaling cascade
that ends with the destruction of the tumor cell.

"Basically we're able to make FOXO1 turn on KLF6, which
tells cancer cells to die," senior author Goutham Narla said in a
telephone interview.

When the researchers gave mice that were injected with human lung
cancer cells trifluoperazine in combination with the targeted lung
cancer drug erlotnib, the tumors shrank much more than in mice treated
with either drug by itself.

Both drugs are already approved by the US Food and Drug
Administration - erlotinib is sold under the brand name Tarceva and
trifluoperazine is marketed under the brand name Stelazine.

Narla says he and his colleagues are working to develop a clinical
trial examining how the two-drug combination fares in human patients.

"One of the advantages to this approach is it can be
immediately translated into clinical trials," Narla says.

Normally, the path to producing a new drug is long and fraught with
failures. But since both drugs have already passed safety tests on their
way to their original FDA approval, trials in humans could start by the
end of 2012, according to Narla.

The anti-psychotic drug could also be potentially used to combat
other kinds of tumors, since the FOXO1 and KLF6 defects found in lung
cancer are also seen in some breast and prostate cancers.

"We can imagine using this combination -- not with Tarceva,
since that's specific to lung cancer -- in other cancers to
activate this particular network," Narla said.

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